Intranodal palisaded myofibroblastoma shows a unique epigenetic profile-first molecular study of their epigenetic and copy number variation profile

Abstract

Intranodal palisaded myofibroblastomas with amianthoid fibers (IPM) are rare mesenchymal neoplasms showing a myofibroblastic differentiation. Histopathologically, they might be difficult to distinguish from schwannoma or other neoplasia with spindle cell morphology, especially on limited biopsies. CTNNB1 gene variants have been detected in at least 50% of tumors. In this study, we determined the methylation profile including the copy number variation profile in a series of six patients. These analyses enabled genes with the highest gains or losses compared to myoblasts and fibroblasts to be identified. We identified a new methylation cluster that is not included in the Heidelberg Sarcoma Classifier so far. Furthermore, significantly differentially hypo- and hypermethylated genes compared to normal myoblasts and fibroblasts were detected in all samples, e.g., ARID5A, MIB2, TRIM58, and others were > 17-fold hypomethylated, while NEDD4, RUNX1, SLC8A1, and others were > 75-fold hypermethylated. Additionally, when combining positive ß-catenin expression and sequencing results, the aberrant/mutant CTNNB1 gene was shown in three tumors (75% of analyzed cases) in this IPM series. The present data provides additional support/adjunct to establish the rare diagnosis of intranodal palisaded myofibroblastomas with amianthoid fibers by molecular testing in diagnostically challenging cases.